The present invention relates to compositions containing therapeutic components, hereinafter TCs, for example, alpha-2-adrenergic agonists. More particularly, the invention relates to such compositions including such TCs, and advantageously one or more other components, in which compositions the TCs preferably have enhanced pharmacokinetic characteristics.
A TC includes any chemical entity, such as a compound, an ion, a complex and the like, which is effective to act on and/or bind to receptors and provide a therapeutic effect. The TC may be an agonist, an antagonist, precursors thereof, metabolites thereof and combinations thereof.
A continuing challenge in providing compositions having TCs is to be able to render such compositions more effective. One way to render the TCs more effective is to enhance their pharmacokinetic dispositions. For example, the dispensed or administered TCs should advantageously be permeable through lipid cell membranes so that the agonist may reach the target receptor to impart a therapeutic effect. One possible reason for why certain TCs permeate poorly through a lipid membrane is that these components may be charged ions at physiological pH.
Although the term “enhancement of pharmacokinetic disposition” as used herein may mean an enhancement in permeability, an enhancement of pharmacokinetic disposition may also mean an enhancement in, for example, bioavailability, sequestration and/or release characteristics of the TCs.
Ion pairing, or complexation, between cations and anions to enhance the movement of ionizable molecules across biologic membranes has been suggested. Nash et al. Skin Pharmacol 5:160-170 (1992) and Ogawa et al. Jpn J Ophthalmol 37:47-55 (1993). However, prior ion complex systems may be inappropriate for use to deliver TCs to certain biological environments, for example, the ophthalmic environment.
There continues to be a need for new compositions that increase the efficacy of therapeutic components.